The role of cyclic AMP in the effect of drugs on smooth muscle motility is a point of considerable controversy at present. One objective of the proposed research will be to determine whether the increases in cyclic AMP concentration reportedly produced by catecholamines in certain types of smooth muscle are causally related to the relaxant effects of the drugs on these muscles. In addition to the catecholamines and their specific blocking agents, other relaxant drugs such as nitroglycerin and papaverine will be investigated. Direct measurements of tissue cycle AMP concentrations will be made in smooth muscles frozen after exposure to relaxant concentrations of these drugs. Similar types of experiments will be carried out using smooth muscle stimulants such as angiotensin, oxytocin and the prostaglandins. These experiments may enable us to decide whether or not cyclic AMP plays a role in the regulation of smooth muscle tone and contractility, as has been recently suggested. Another major phase of the proposed research will be to investigate biochemical changes which could result in increased energy production during spontaneous contractions in smooth muscle. Phosphorylase activity has been shown to increase during such contractions, and experiments have been designed to determine whether phosphofructokinase activity also increases under these conditions. The effects of calcium on the activation of these enzymes during contraction will be investigated. These experiments may provide some support for a role of calcium in the activation and inactivation of certain glycolytic enzymes during contraction and relaxation of smooth muscle. This would provide a mechanism whereby energy production within the muscle could be altered to conform to periods of altered mechanical activity of the muscles (i.e. during labor in pregnant uterus).